Biomedical subjects

J G Müller

Publications and source records attributed to J G Müller.

40 records · Page 3Linked to original sources

PubMedDate not supplied

Impact of various simian immunodeficiency virus variants on induction and nature of neuropathology in macaques.

To investigate the possible influence of virus tropism on SIV-induced neuropathogenesis, macaques were infected with molecularly cloned SIVmac239 which replicates poorly in cultured macrophages, with SIVmac251/32H which is a macrophage-tropic biologic clone, and with SIVmac251/MPBMC which is an early passage of 32H with enhanced replication competence in macrophages. We found that inflammatory as well as neuropathologic changes were identical in all clinically affected animals, irrespective of the in vitro tropism of the inocula. Moribund animals exhibited SIV encephalitis characterized by overt infection of macrophages/microglia inside the CNS parenchyma. Additionally, neuropathology of moribund animals was characterized by extraparenchymal immunopathology (meninges, perivascular space, choroid plexus stroma) and subtle white matter degeneration with glial changes, often associated with infected macrophages in situ (except in leukoencephalopathy). However, in animals inoculated with the lymphocyte-tropic and enhanced macrophage-tropic inocula, microglia but not blood-derived macrophages were the primary cells infected. Altogether, our results underline the significance of macrophage infection for the development of SIV encephalitis, and suggest that SIVmac239 either undergoes a change in cell tropism in vivo that results in the ability to replicate in macrophages, or else macrophages become more permissive to infection by this virus in the terminal stage of immunosuppressive disease.

Animals↗

PubMedDate not supplied

The thymic epithelial reticulum and interdigitating cells in SIV-induced thymus atrophy and its comparison with other forms of thymus involution.

Alterations in the thymus were investigated in the early course of SIV infection of rhesus monkeys and compared with age-related and acute accidental thymus atrophy. The SIV-induced pathology was characterized by shrinkage of the thymic parenchyma and capsule, whereas in age-related thymus atrophy, the size of the capsule remained unaltered and the emerging space was filled by fatty tissue. Acute accidental thymus involution is characterized by massive cell death of the thymocytes, but there was no increase in pycnotic thymocytes either in SIV-induced or in age-related thymus atrophy. Ultrastructural analysis revealed no major differences between the juvenile control and the aged thymus. In contrast, SIV-induced thymus atrophy exhibited severe alterations of the epithelial cells of the cortex and the interdigitating dendritic cells, which were not found in the aged thymus nor in the juvenile control cortex.

Aging↗

PubMedDate not supplied

Detection of SIV in rhesus monkey thymus stroma cell cultures.

To clarify the pathogenesis of SIV-induced thymus atrophy, the presence of SIV within thymus stromal cell cultures (epithelial cells, IDC, macrophages or fibroblasts) was investigated. The material studied consisted of 15 thymus specimens of rhesus macaques infected with SIVmac251 (2-4 months postinoculation). No viral antigen was detected, either in the cultures, by immunohistochemistry, or in cell culture supernatants, by ELISA (p17 antigen), and no viral RNA was detected by in situ hybridization. Only after coculture with the C8166 cell line, was virus detected in 2 out of 15 stroma cultures. The fact that the virus could only be detected after several passages of coculture with the C8166 cell line indicates that the virus exists in the thymus stroma cells in the form of proviral DNA. The infection of thymus stromal cells may contribute to the destruction of the thymus microenvironment and to the SIV-induced thymus atrophy.

Animals↗

PubMedDate not supplied

Prognostic relevance of p53 in node negative breast cancer.

In a retrospective study, immunohistochemical determinations of p53 were performed on paraffinised tissue sections of 243 patients with node negative breast cancer. These patients were primary treated in the years 1980-1986 at the UFK-Würzburg. A complete follow up could be performed in 92% of all cases. The median follow up is at 102 month. The results have been correlated to other prognostic criteria and to the clinical course of the patients. In 77 of the 243 cases a positive immunohistochemical staining for p53 (31.7%) could be found. In 42 (17.3%) cancer specimens the p53 expression was over 5%. A significant correlation was found between p53 and tumour size (p = 0.05), ploidy (p < 0.001) and dynamic parameters of the cell cycle (S-phase-fraction, MIB1: p < 0.001). In univariate and multivariate analysis the expression of p53 did not effect disease-free or over-all survival of patients with node negative breast cancer.

Breast Neoplasms↗